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| | ==Crystal Structure of catalytic domain of PTPRQ== | | ==Crystal Structure of catalytic domain of PTPRQ== |
| - | <StructureSection load='4ikc' size='340' side='right' caption='[[4ikc]], [[Resolution|resolution]] 1.56Å' scene=''> | + | <StructureSection load='4ikc' size='340' side='right'caption='[[4ikc]], [[Resolution|resolution]] 1.56Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ikc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IKC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ikc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IKC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.56Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPRQ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ikc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ikc OCA], [https://pdbe.org/4ikc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ikc RCSB], [https://www.ebi.ac.uk/pdbsum/4ikc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ikc ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ikc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ikc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ikc RCSB], [http://www.ebi.ac.uk/pdbsum/4ikc PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PTPRQ_HUMAN PTPRQ_HUMAN]] Autosomal recessive nonsyndromic sensorineural deafness type DFNB. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/PTPRQ_HUMAN PTPRQ_HUMAN] Autosomal recessive nonsyndromic sensorineural deafness type DFNB. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTPRQ_HUMAN PTPRQ_HUMAN]] Phosphatidylinositol phosphatase required for auditory function. May act by regulating the level of phosphatidylinositol 4,5-bisphosphate (PIP2) level in the basal region of hair bundles. Can dephosphorylate a broad range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5-trisphosphate and most phosphatidylinositol monophosphates and diphosphates. Phosphate can be hydrolyzed from the D3 and D5 positions in the inositol ring. Has low tyrosine-protein phosphatase activity; however, the relevance of such activity in vivo is unclear. Plays an important role in adipogenesis of mesenchymal stem cells (MSCs). Regulates the phosphorylation state of AKT1 by suppressing the phosphatidylinositol 3,4,5-trisphosphate (PIP3) level in MSCs and preadipocyte cells.<ref>PMID:19351528</ref> | + | [https://www.uniprot.org/uniprot/PTPRQ_HUMAN PTPRQ_HUMAN] Phosphatidylinositol phosphatase required for auditory function. May act by regulating the level of phosphatidylinositol 4,5-bisphosphate (PIP2) level in the basal region of hair bundles. Can dephosphorylate a broad range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5-trisphosphate and most phosphatidylinositol monophosphates and diphosphates. Phosphate can be hydrolyzed from the D3 and D5 positions in the inositol ring. Has low tyrosine-protein phosphatase activity; however, the relevance of such activity in vivo is unclear. Plays an important role in adipogenesis of mesenchymal stem cells (MSCs). Regulates the phosphorylation state of AKT1 by suppressing the phosphatidylinositol 3,4,5-trisphosphate (PIP3) level in MSCs and preadipocyte cells.<ref>PMID:19351528</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4ikc" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Protein-tyrosine-phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Kim, S J]] | + | [[Category: Kim SJ]] |
| - | [[Category: Ryu, S E]] | + | [[Category: Ryu SE]] |
| - | [[Category: Yu, K R]] | + | [[Category: Yu KR]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Phosphatase]]
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| Structural highlights
Disease
PTPRQ_HUMAN Autosomal recessive nonsyndromic sensorineural deafness type DFNB. The disease is caused by mutations affecting the gene represented in this entry.
Function
PTPRQ_HUMAN Phosphatidylinositol phosphatase required for auditory function. May act by regulating the level of phosphatidylinositol 4,5-bisphosphate (PIP2) level in the basal region of hair bundles. Can dephosphorylate a broad range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5-trisphosphate and most phosphatidylinositol monophosphates and diphosphates. Phosphate can be hydrolyzed from the D3 and D5 positions in the inositol ring. Has low tyrosine-protein phosphatase activity; however, the relevance of such activity in vivo is unclear. Plays an important role in adipogenesis of mesenchymal stem cells (MSCs). Regulates the phosphorylation state of AKT1 by suppressing the phosphatidylinositol 3,4,5-trisphosphate (PIP3) level in MSCs and preadipocyte cells.[1]
Publication Abstract from PubMed
Unlike other classical protein tyrosine phosphatases (PTPs), PTPRQ (PTP receptor type Q) has dephosphorylating activity towards phosphatidylinositide (PI) substrates. Here, the structure of the catalytic domain of PTPRQ was solved at 1.56 A resolution. Overall, PTPRQ adopts a tertiary fold typical of other classical PTPs. However, the disordered M6 loop of PTPRQ surrounding the catalytic core and the concomitant absence of interactions of this loop with residues in the PTP loop results in a flat active-site pocket. On the basis of structural and biochemical analyses, it is proposed that this structural feature might facilitate the accommodation of large substrates, making it suitable for the dephosphorylation of PI substrates. Moreover, subsequent kinetic experiments showed that PTPRQ has a strong preferences for PI(3,4,5)P3 over other PI substrates, suggesting that its regulation of cell survival and proliferation reflects downregulation of Akt signalling.
Structural basis for the dephosphorylating activity of PTPRQ towards phosphatidylinositide substrates.,Yu KR, Kim YJ, Jung SK, Ku B, Park H, Cho SY, Jung H, Chung SJ, Bae KH, Lee SC, Kim BY, Erikson RL, Ryu SE, Kim SJ Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1522-9. doi:, 10.1107/S0907444913010457. Epub 2013 Jul 19. PMID:23897475[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jung H, Kim WK, Kim do H, Cho YS, Kim SJ, Park SG, Park BC, Lim HM, Bae KH, Lee SC. Involvement of PTP-RQ in differentiation during adipogenesis of human mesenchymal stem cells. Biochem Biophys Res Commun. 2009 May 29;383(2):252-7. doi:, 10.1016/j.bbrc.2009.04.001. Epub 2009 Apr 5. PMID:19351528 doi:10.1016/j.bbrc.2009.04.001
- ↑ Yu KR, Kim YJ, Jung SK, Ku B, Park H, Cho SY, Jung H, Chung SJ, Bae KH, Lee SC, Kim BY, Erikson RL, Ryu SE, Kim SJ. Structural basis for the dephosphorylating activity of PTPRQ towards phosphatidylinositide substrates. Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1522-9. doi:, 10.1107/S0907444913010457. Epub 2013 Jul 19. PMID:23897475 doi:http://dx.doi.org/10.1107/S0907444913010457
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